Download DATA SHEET FLIXOTIDE® Inhaler

DATA SHEET
FLIXOTIDE ® Inhaler
Fluticasone propionate Inhaler (CFC-Free) (50, 125 or 250
micrograms per actuation).
Qualitative and quantitative composition
FLIXOTIDE 50 Inhaler is a pressurised metered-dose inhaler which delivers
50mcg of fluticasone propionate per actuation into the mouthpiece of a
specially designed actuator. Each canister supplies 120 actuations.
FLIXOTIDE 125 Inhaler is a pressurised metered-dose inhaler which delivers
125mcg of fluticasone propionate per actuation into the mouthpiece of a
specially designed actuator. Each canister supplies 120 actuations.
FLIXOTIDE 250 Inhaler is a pressurised metered-dose inhaler which delivers
250mcg of fluticasone propionate per actuation. Each canister supplies 120
actuations.
Pharmaceutical form
Pressurised metered-dose aerosol.
Clinical particulars
Therapeutic Indications
Asthma:Fluticasone propionate has a marked anti-inflammatory effect in the lungs.
It reduces symptoms and exacerbations of asthma in patients previously
treated with bronchodilator alone or with other prophylactic therapy.
Severe asthma requires regular medical assessment as death may occur.
Patients with severe asthma have constant symptoms and frequent
exacerbations, with limited physical capacity, and PEF values below 60%
predicted at baseline with greater than 30% variability, usually not returning
entirely to normal after a bronchodilator. These patients will require high dose
inhaled (see dosage instructions) or oral corticosteroid therapy. Sudden
worsening of symptoms may require increased corticosteroid dosage which
should be administered under urgent medical supervision.
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Adults:Prophylactic management in:
- Mild asthma (PEF values greater than 80% predicted at baseline with less
than 20% variability): Patients requiring intermittent symptomatic
bronchodilator asthma medication on more than an occasional basis.
- Moderate asthma (PEF values 60-80% predicted at baseline with 20-30%
variability): Patients requiring regular asthma medication and patients with
unstable or worsening asthma on currently available prophylactic therapy
or bronchodilator alone.
- Severe asthma (PEF values less than 60% predicted at baseline with
greater than 30% variability): Patients with severe chronic asthma. On
introduction of inhaled fluticasone propionate many patients who are
dependent on systemic corticosteroids for adequate control of symptoms
may be able to reduce significantly or to eliminate their requirement for oral
corticosteroids.
Children:Any child who requires preventive asthma medication, including patients not
controlled on currently available prophylactic medication.
Posology and Method of Administration
FLIXOTIDE Inhaler (CFC-Free) is for oral inhalation only.
The diagnosis and treatment of asthma should be kept under regular review.
Patients should be made aware of the prophylactic nature of therapy with
inhaled fluticasone propionate and that it should be taken regularly even when
they are asymptomatic. The onset of therapeutic effect is 4 to 7 days,
although some benefit may be apparent as soon as 24 hours for patients who
have not previously received inhaled steroids.
The dosage of fluticasone propionate should be adjusted according to the
individual response.
If patients find that relief with short-acting bronchodilator treatment becomes
less effective or they need more inhalations than usual, medical attention
must be sought.
It is intended that each prescribed dose is given by a minimum of 2
inhalations.
In patients who find co-ordination of a pressurised metered dose inhaler
difficult, a spacer may be used with FLIXOTIDE Inhaler (CFC-Free).
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Asthma:
Adults and children over 16 years of age:
100 to 1000mcg twice daily.
Patients should be given a starting dose of inhaled fluticasone propionate
which is appropriate for the severity of their disease:Mild asthma:
-
100 to 250mcg twice daily.
Moderate asthma: -
250 to 500mcg twice daily.
Severe asthma:
500 to 1000mcg twice daily.
-
The dose may then be adjusted until control is achieved or reduced to the
minimum effective dose, according to the individual response.
Alternatively, the starting dose of fluticasone propionate may be gauged at
half the total daily dose of beclomethasone dipropionate or equivalent as
administered by metered-dose inhaler.
Children over 4 years of age:-
50 to 200mcg twice daily.
Many children’s asthma will be well controlled using the 50 to 100mcg twice
daily dosing regime. For those patients whose asthma is not sufficiently
controlled, additional benefit may be obtained by increasing the dose up to
200mcg twice daily.
Children should be given a starting dose of inhaled fluticasone propionate
which is appropriate for the severity of their disease.
The dose may then be adjusted until control is achieved, or reduced to the
minimum effective dose, according to the individual response.
This presentation of fluticasone propionate may not offer the required
paediatric dose, in which case an alternative presentation of fluticasone
propionate should be considered (e.g. dry powder inhalers).
Children aged 1 to 4 years:-
100mcg twice daily administered via a
paediatric spacer device with a face mask.
Inhaled fluticasone propionate is of benefit to younger children in the control
of frequent and persistent asthma symptoms.
Clinical trials in 1 to 4 year old children have shown that the optimal control of
asthma symptoms is achieved with 100mcg twice daily. Higher doses of
inhaled fluticasone propionate are required in younger children compared to
older children because of reduced efficiency of drug delivery due to smaller
airways, use of a spacer device and increased nasal breathing.
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Special patient groups:There is no need to adjust the dose in elderly patients or in those with hepatic
or renal impairment.
Contra-indications
Hypersensitivity to any ingredient of the preparation.
Special Warnings and Special Precautions for Use
Increasing use of short-acting inhaled β2-agonists to control asthma
symptoms indicates deterioration of asthma control. Under these conditions,
the patient's therapy plan should be reassessed. Sudden and progressive
deterioration in asthma control is potentially life-threatening and consideration
should be given to increasing corticosteroid dosage. In patients considered at
risk, daily peak flow monitoring may be instituted.
Patients' inhaler technique should be checked to make sure that inhaler
actuation is synchronised with inspiration to ensure optimum delivery of the
medicine to the lungs.
Systemic effects may occur with any inhaled corticosteroid, particularly at high
doses prescribed for long periods; these effects are much less likely to occur
than with oral corticosteroids (see Overdose). Possible systemic effects
include Cushing’s syndrome, Cushingoid features, adrenal suppression,
growth retardation and (very rarely) behavioural disturbances in children and
adolescents, decrease in bone mineral density, cataract and glaucoma. It is
important, therefore, that the dose of inhaled corticosteroid is titrated to the
lowest dose at which effective control is maintained (see Undesirable Effects).
It is recommended that the height of children receiving prolonged treatment
with inhaled corticosteroid is regularly monitored.
The possibility of impaired adrenal response should always be considered in
emergency situations (including surgery), and also in elective situations likely
to produce stress, especially in patients taking high doses for an extended
duration of time. Additional corticosteroid treatment appropriate to a given
clinical situation must be considered (see Overdosage).
Because of the possibility of impaired adrenal response, patients transferring
from oral steroid therapy to inhaled fluticasone propionate therapy should be
treated with special care, and adrenocortical function regularly monitored.
Following introduction of inhaled fluticasone propionate, withdrawal of
systemic therapy should be gradual and patients encouraged to carry a
steroid warning card indicating the possible need for additional therapy in
times of stress.
In rare cases inhaled therapy may unmask underlying eosinophilic conditions
(e.g. Churg Strauss syndrome). These cases have usually been associated
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with reduction or withdrawal of oral corticosteroid therapy. A direct causal
relationship has not been established.
Similarly replacement of systemic steroid treatment with inhaled therapy may
unmask allergies such as allergic rhinitis or eczema previously controlled by
the systemic drug.
Treatment with FLIXOTIDE Inhaler (CFC-Free) should not be stopped
abruptly.
As with all inhaled corticosteroids, special care is necessary in patients with
active or quiescent pulmonary tuberculosis.
A drug interaction study in healthy subjects has shown that ritonavir (a highly
potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone
propionate plasma concentrations, resulting in markedly reduced serum
cortisol concentrations. During post-marketing use, there have been reports of
clinically significant drug interactions in patients receiving fluticasone
propionate and ritonavir, resulting in systemic corticosteroid effects including
Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of
fluticasone propionate and ritonavir should be avoided, unless the potential
benefit to the patient outweighs the risk of systemic corticosteroid side-effects.
There have been very rare reports of increases in blood glucose levels (see
Undesirable Effects) and this should be considered when prescribing to
patients with a history of diabetes mellitus.
As with other inhalation therapy paradoxical bronchospasm may occur with an
immediate increase in wheezing after dosing. This should be treated
immediately with a fast and short-acting inhaled bronchodilator. Fluticasone
propionate should be discontinued immediately, the patient assessed and
alternative therapy instituted if necessary (see Adverse Reactions).
Use During Pregnancy and Lactation
Fertility
There are no data on human fertility. Animal studies indicate no effects of
fluticasone propionate or salmeterol xinofoate on male or female fertility.
Pregnancy
There are limited data in pregnant women. Administration of fluticasone
propionate during pregnancy should only be considered if the expected
benefit on the mother is greater than any possible risk to the foetus.
An observational retrospective epidemiological cohort study utilising electronic
health records from the United Kingdom was conducted to evaluate the risk of
major congenital malformations (MCMs) following first trimester exposure to
inhaled fluticasone propionate alone and salmeterol-fluticasone propionate
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relative to non-fluticasone propionate containing inhaled corticosteroids. No
placebo comparator was included in this study.
Within the asthma cohort of 5362 first trimester inhaled corticosteroidsexposed pregnancies, 131 diagnosed MCMs were identified; 1612 (30%)
were exposed to fluticasone propionate or salmeterol-fluticasone propionate
of which 42 diagnosed MCMs were identified. The adjusted odds ratio for
MCMs diagnosed by 1 year was 1.1 (95%CI: 0.5 – 2.3) for fluticasone
propionate exposed vs non-fluticasone propionate inhaled corticosteroid
exposed women with moderate asthma and 1.2 (95%CI: 0.7 – 2.0) for women
with considerable to severe asthma. No difference in the risk of MCMs was
identified following first trimester exposure to fluticasone propionate alone
versus salmeterol-fluticasone propionate. Absolute risks of MCM across the
asthma severity strata ranged from 2.0 to 2.9 per 100 fluticasone propionateexposed pregnancies which is comparable to results from a study of 15,840
pregnancies unexposed to asthma therapies in the General Practice
Research Database (2.8 MCM events per 100 pregnancies).
Results from the retrospective epidemiological study did not find any
increased risk of major congenital malformations (MCMs) following exposure
to fluticasone propionate when compared to other inhaled corticosteroids,
during the first trimester of pregnancy.
Reproductive studies in animals have shown only those effects characteristic
of glucocorticosteroids at systemic exposure in excess of those seen at the
recommended inhaled therapeutic dose.
Lactation
The excretion of fluticasone propionate into human breast milk has not been
investigated. When measurable plasma levels were obtained in lactating
laboratory rats following subcutaneous administration there was evidence of
fluticasone propionate in the breast milk. However, plasma levels in patients
following inhaled application of fluticasone propionate at recommended doses
are likely to be low.
Administration during lactation should only be considered if the expected
benefit to the mother is greater than any possible risk to the child.
Effects on Ability to Drive and Use Machines
Fluticasone propionate is unlikely to produce an effect.
Interaction with Other Medicinal Products and Other Forms of Interaction
Under normal circumstances, low plasma concentrations of fluticasone
propionate are achieved after inhaled dosing, due to extensive first pass
metabolism and high systemic clearance mediated by cytochrome P450 3A4
in the gut and liver. Hence, clinically significant drug interactions mediated by
fluticasone propionate are unlikely.
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A drug interaction study in healthy subjects has shown that ritonavir (a highly
potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone
propionate plasma concentrations, resulting in markedly reduced serum
cortisol concentrations. During post-marketing use, there have been reports of
clinically significant drug interactions in patients receiving fluticasone
propionate and ritonavir, resulting in systemic corticosteroid effects including
Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of
fluticasone propionate and ritonavir should be avoided, unless the potential
benefit to the patient outweighs the risk of systemic corticosteroid side-effects.
Studies have shown that other inhibitors of cytochrome P450 3A4 produce
negligible (erythromycin) and minor (ketoconazole) increases in systemic
exposure to fluticasone propionate without notable reductions in serum
cortisol concentrations. Nevertheless, care is advised when co-administering
potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole) as there is
potential for increased systemic exposure to fluticasone propionate.
Undesirable Effects
Adverse events are listed below by system organ class and frequency.
Frequencies are defined as: very common (≥1/10), common (≥1/100 to
<1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very
rare (<1/10,000) including isolated reports. Very common, common and
uncommon events were generally determined from clinical trial data. Rare
and very rare events were generally determined from spontaneous data.
Infections and infestations
Very common:
Candidiasis of mouth and throat
Candidiasis of the mouth and throat (thrush) occurs in some patients. Such
patients may find it helpful to rinse out their mouth with water after using the
inhaler. Symptomatic candidiasis can be treated with topical anti-fungal
therapy whilst still continuing with the FLIXOTIDE Inhaler (CFC-Free).
Rare:
Oesophageal candidiasis
Immune system disorders
Hypersensitivity reactions with the following manifestations have been
reported:
Uncommon: Cutaneous hypersensitivity reactions
Very rare:
Angioedema (mainly facial and oropharyngeal oedema),
respiratory symptoms (dyspnoea and/or bronchospasm) and
anaphylactic reactions
Endocrine disorders
Possible systemic effects include (see Special Warnings and Special
Precautions for Use):
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Very rare:
Cushing’s syndrome, Cushingoid features, adrenal suppression,
growth retardation, decreased bone mineral density, cataract
and glaucoma
Metabolism and nutrition disorders
Very rare:
Hyperglycaemia
Psychiatric disorders
Very rare:
Anxiety, sleep disorders and behavioural changes, including
hyperactivity and irritability (predominantly in children)
Respiratory, thoracic and mediastinal disorders
Common:
Hoarseness
In some patients inhaled fluticasone propionate may cause hoarseness. It
may be helpful to rinse out the mouth with water immediately after inhalation
Very rare:
Paradoxical bronchospasm (see Warnings and Precautions)
Skin and subcutaneous tissue disorders
Common:
Contusions
Overdose
Acute inhalation of fluticasone propionate doses in excess of those approved
may lead to temporary suppression the hypothalamic-pituitary-adrenal axis.
This does not usually require emergency action as normal adrenal function
typically recovers within a few days.
If higher than approved doses are continued over prolonged periods,
significant adrenocortical suppression is possible. There have been very rare
reports of acute adrenal crisis occurring in children exposed to higher than
approved doses (typically 1000mcg daily and above), over prolonged periods
(several months or years); observed features included hypoglycaemia and
sequelae of decreased consciousness and/or convulsions. Situations which
could potentially trigger acute adrenal crisis include exposure to trauma,
surgery, infection or any rapid reduction in dosage. Patients receiving higher
than approved doses should be managed closely and the dose reduced
gradually.
Pharmacological properties
Pharmacodynamic properties
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Fluticasone propionate given by inhalation at recommended doses has a
potent glucocorticoid anti-inflammatory action within the lungs which results in
reduced symptoms and exacerbations of asthma.
Pharmacokinetic properties
The absolute bioavailability of fluticasone propionate for each of the available
inhaler devices has been estimated from within and between study
comparisons of inhaled and intravenous pharmacokinetic data. In healthy
adult subjects the absolute bioavailability has been estimated for Flixotide
Accuhaler (7.8%) and Flixotide Inhaler (10.9%) respectively. In patients with
asthma a lesser degree of systemic exposure to inhaled fluticasone
propionate has been observed. Systemic absorption occurs mainly through
the lungs and is initially rapid then prolonged. The remainder of the inhaled
dose may be swallowed but contributes minimally to systemic exposure due
to the low aqueous solubility and pre-systemic metabolism, resulting in oral
availability of less than 1%. There is a linear increase in systemic exposure
with increasing inhaled dose. The disposition of fluticasone propionate is
characterised by high plasma clearance (1150mL/min), a large volume of
distribution at steady-state (approximately 300L) and a terminal half-life of
approximately 8 hours. Plasma protein binding is moderately high (91%).
Fluticasone propionate is cleared very rapidly from the systemic circulation,
principally by metabolism to an inactive carboxylic acid metabolite, by the
cytochrome P450 enzyme CYP3A4. The renal clearance of fluticasone
propionate is negligible (<0.2%) and less than 5% as the metabolite. Care
should be taken when co-administering known CYP3A4 inhibitors, as there is
potential for increased systemic exposure to fluticasone propionate.
Preclinical safety data
Toxicology has shown only those class effects typical of potent
corticosteroids, and these only at doses in excess of those proposed for
therapeutic use. No novel effects were identified in repeat dose toxicity tests,
reproductive studies or teratology studies. Fluticasone propionate is devoid of
mutagenic activity in-vitro and in-vivo and showed no tumorigenic potential in
rodents. It is both non-irritant and non-sensitising in animal models.
The non-CFC propellant, HFA 134a, has been shown to have no toxic effect
at very high vapour concentrations, far in excess of those likely to be
experienced by patients, in a wide range of animal species exposed daily for
periods of two years.
Pharmaceutical particulars
List of excipients
HFA 134a
Incompatibilities
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None reported.
Shelf life
2 years.
Special precautions for storage
Replace the mouthpiece cover firmly and snap it into position.
FLIXOTIDE Inhaler (CFC-Free) should be stored below 30°C.
Protect from frost and direct sunlight.
As with most inhaled medications in pressurised canisters, the therapeutic
effect of this medication may decrease when the canister is cold.
The canister should not be punctured, broken or burnt even when apparently
empty.
Nature and contents of container
FLIXOTIDE Inhaler (CFC-Free) comprises a suspension of fluticasone
propionate in the non-CFC propellant HFA 134a. The suspension is contained
in an aluminium alloy can sealed with a metering valve. The canisters are
fitted into plastic actuators incorporating an atomising orifice and fitted with
dustcaps. FLIXOTIDE Inhaler (CFC-Free) has been formulated in three
strengths, 50mcg, 125mcg or 250mcg of fluticasone propionate per actuation,
120 actuations per inhaler.
Instructions for use/handling
Testing your inhaler:Before using for the first time or if your inhaler has not been used for a week
or more remove the mouthpiece cover by gently squeezing the sides of the
cover, shake the inhaler well, and release two puffs into the air to make sure
that it works.
Using your inhaler:1.
Remove the mouthpiece cover by gently squeezing the sides of the
cover.
2.
Check inside and outside of the inhaler including the mouthpiece for
the presence of loose objects.
3.
Shake the inhaler well to ensure that any loose objects are removed
and that the contents of the inhaler are evenly mixed.
4.
Hold the inhaler upright between fingers and thumb with your thumb on
the base, below the mouthpiece.
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5.
Breathe out as far as is comfortable and then place the mouthpiece in
your mouth between your teeth and close your lips around it but do not
bite it.
6.
Just after starting to breathe in through your mouth press down on the
top of the inhaler to release fluticasone propionate while still breathing
in steadily and deeply.
7.
While holding your breath, take the inhaler from your mouth and take
your finger from the top of the inhaler. Continue holding your breath for
as long as is comfortable.
8.
If you are to take further puffs keep the inhaler upright and wait about
half a minute before repeating steps 3 to 7.
9.
Afterwards, rinse your mouth with water and spit it out.
10.
Replace the mouthpiece cover by firmly pushing and snapping the cap
into position.
IMPORTANT:Do not rush stages 5, 6 and 7. It is important that you start to breathe in as
slowly as possible just before operating your inhaler.
Practise in front of a mirror for the first few times. If you see "mist" coming
from the top of your inhaler or the sides of your mouth you should start again
from stage 2.
If your doctor has given you different instructions for using your inhaler,
please follow them carefully. Tell your doctor if you have any difficulties.
Children:Young children may need help and an adult may need to operate the inhaler
for them. Encourage the child to breathe out and operate the inhaler just after
the child starts to breathe in. Practice the technique together. Older children
or people with weak hands should hold the inhaler with both hands. Put the
two forefingers on top of the inhaler and both thumbs on the base below the
mouthpiece.
Cleaning:Your inhaler should be cleaned at least once a week.
1.
Remove the mouthpiece cover.
2.
Do not remove the canister from the plastic casing.
3.
Wipe the inside and outside of the mouthpiece with a dry cloth or
tissue.
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4.
Replace the mouthpiece cover.
DO NOT PUT THE METAL CANISTER INTO WATER.
Medicines classification
Prescription Only Medicine
Name and address
GlaxoSmithKline NZ Limited
Private Bag 106600
Downtown
Auckland
NEW ZEALAND
Telephone: (09) 367 2900
Facsimile: (09) 367 2910
Date of Preparation
5 October 2015
Version: 6.0
FLIXOTIDE ® is a registered trade mark of the GlaxoSmithKline group of
companies.
© This Data Sheet is copyrighted to GlaxoSmithKline and may be reproduced but not altered
in any way.
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